Over 150,000 vein graft procedures are performed annually in the United States. Of the grafts which fail, 25% do so because of adverse changes occurring within the grafted vein itself. The long-term objective of this proposal is to study the pathogenesis of the adverse morphologic-changes occurring within these grafts, with the aim to devise methods of prevention. Transplantation of a vein to the arterial circulation invariably results in desquamation of the venous endothelium from large areas. This luminal surface is subsequently covered with blood elements, principally platelets and leukocytes. It is the specific aim of the studies in this proposal to evaluate the role of the endothelium, blood platelets, mononuclear cells,and granulocytes in the morphologic changes that occur in veins transplanted into the arterial circulation. This will be accomplished by labelling these cells with radioactive tracers and observing their accumulation and disappearance on the surface of grafts placed in animals. These observations will be correlated with the morphologic changes in the intima of vein grafts over time. The effect of anticoagulant and antiplatelet drugs will be tested in these systems, with the long-term goal of establishing methods to minimize the deleterious changes that occur in vein grafts, and thereby increase the success of vein graft surgery.